Barrett's esophagus is felt to be the precursor lesion to esophageal adenocarcinoma which is the most rapidly increasing cancer in males. Clinical management decisions concerning this condition are based on biopsies of the Barrett's mucosa which are difficult to adequately obtain and interpret, costly to examine histologically, and often miss lesions of significance. The use of exfoliated cells from Barrett's esophagus collected with brush cytology has the potential to rapidly assess its malignant potential. We propose to investigate two novel methods to assess exfoliated cells to increase the sensitivity for malignant changes. It is our hypothesis that either digital image analysis (DIA) or fluorescent in situ hybridization (FISH) performed on exfoliated cells will be able to predict cancer development in Barrett's esophagus. We have demonstrated that both correlate well with histology from surveillance biopsies with FISH being significantly superior to DIA. This was done using an investigational set of twelve probes that targeted multiple important loci for cancer progression in Barrett's esophagus. We have taken this information to select four very targeted loci that we believe should allow us to develop a high-throughput test to determine cancer risk from exfoliated cells from Barrett's esophagus. Our primary aim will be to test this novel 4 probe FISH test against DIA in cytology specimens using the results of histology from surveillance biopsy for our reference. This will be accomplished by performing FISH and DIA on cytological specimens from patients with known Barrett's esophagus. A secondary aim will be to determine if cytological collection devices that acquire significantly different numbers of exfoliated cells will yield different results using FISH or DIA. Commercially available cytological brushes can vary as much as 6-fold in their ability to collect exfoliated cells. We have developed a novel cytology net that can acquire five times as many cells as the brushes. We propose to randomize the type cytology collection device used to collect the exfoliated cells to determine if this affects the results of DIA or FISH. The results of this study can potentially change the method by which physicians can evaluate the cancer risk of patients with Barrett's esophagus. It is hoped that by using cytology assessed with FISH or DIA, better information of cancer risk can be obtained so that patients can have cancers detected earlier or be treated to prevent cancer in order to decrease esophageal cancer related deaths. This is an innovative method by which a physician can diagnose hidden areas of cancer within patients who are at a high risk of developing esophageal cancer. [unreadable] [unreadable] [unreadable]